Negative regulation of DNA replication by the retinoblastoma protein is mediated by its association with MCM7.
A yeast two-hybrid screen was employed to identify human proteins that specifically bind the amino-terminal 400 amino acids of the retinoblastoma (Rb) protein. Two independent cDNAs resulting from this screen were found to encode the carboxy-terminal 137 amino acids of MCM7, a member of a family of proteins that comprise ... replication licensing factor. Full-length Rb and MCM7 form protein complexes in vitro, and the amino termini of two Rb-related proteins, p107 and p130, also bind MCM7. Protein complexes between Rb and MCM7 were also detected in anti-Rb immunoprecipitates prepared from human cells. The amino-termini of Rb and p130 strongly inhibited DNA replication in an MCM7-dependent fashion in a Xenopus in vitro DNA replication assay system. These data provide the first evidence that Rb and Rb-related proteins can directly regulate DNA replication and that components of licensing factor are targets of the products of tumor suppressor genes.
Mesh Terms:
Amino Acid Sequence, Animals, Cell Cycle Proteins, DNA Replication, DNA, Complementary, DNA-Binding Proteins, Humans, Male, Molecular Sequence Data, Nuclear Proteins, Ovum, Peptide Fragments, Phosphoproteins, Protein Binding, Proteins, Recombinant Proteins, Retinoblastoma Protein, Retinoblastoma-Like Protein p107, Retinoblastoma-Like Protein p130, Spermatozoa, Xenopus, Xenopus Proteins
Amino Acid Sequence, Animals, Cell Cycle Proteins, DNA Replication, DNA, Complementary, DNA-Binding Proteins, Humans, Male, Molecular Sequence Data, Nuclear Proteins, Ovum, Peptide Fragments, Phosphoproteins, Protein Binding, Proteins, Recombinant Proteins, Retinoblastoma Protein, Retinoblastoma-Like Protein p107, Retinoblastoma-Like Protein p130, Spermatozoa, Xenopus, Xenopus Proteins
Mol. Cell. Biol.
Date: May. 01, 1998
PubMed ID: 9566894
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